1-16148628-C-T

Position:

chr1-16148628-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004431.5(EPHA2):c.573G>A(p.Leu191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,607,608 control chromosomes in the GnomAD database, including 86,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6602 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80154 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.414

Variant links:

Genes affected

EPHA2 (HGNC:3386): (EPH receptor A2) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]

EPHA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-16148628-C-T is Benign according to our data. Variant chr1-16148628-C-T is described in ClinVar as [Benign]. Clinvar id is 259394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16148628-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.414 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.573G>A	p.Leu191=	synonymous_variant	3/17	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 linkuse as main transcript	c.573G>A	p.Leu191=	synonymous_variant	3/17	1	NM_004431.5	ENSP00000351209	P1	P29317-1
EPHA2	ENST00000461614.1 linkuse as main transcript	n.625G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42280

AN:

151972

Hom.:

6594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.298

AC:

73530

AN:

246468

Hom.:

11885

AF XY:

0.306

AC XY:

40984

AN XY:

133760

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0176

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.324

AC:

472241

AN:

1455518

Hom.:

80154

Cov.:

AF XY:

0.326

AC XY:

236464

AN XY:

724360

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.278

AC:

42299

AN:

152090

Hom.:

6602

Cov.:

AF XY:

0.277

AC XY:

20598

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.318

Hom.:

4086

Bravo

AF:

0.274

Asia WGS

AF:

0.192

AC:

668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 6 multiple types

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.3

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over